Beta-lactam analogues of oxotremorine. 3- and 4-methyl-substituted 2-azetidinones.
Four beta-lactam analogues (8-11) of oxotremorine were synthesized and assayed for muscarinic and antimuscarinic activity on the isolated guinea pig ileum. The pharmacological results were compared with those obtained previously with the beta-lactam analogue 7 and the 3-, 4-, and 5-methyl-substituted 2-pyrrolidones 2-6. The new compounds were less potent than the corresponding 2-pyrrolidones, regardless of whether they showed agonist (10 and 11), partial agonist (8), or antagonist properties (9) in the ileum assay. The agonists 10 and 11 were about 200-fold less potent than 7. Compounds 8-11 also were less potent than the similarly substituted 2-pyrrolidones in inhibiting the binding of the muscarinic antagonist (-)-[3H]-N-methylscopolamine in homogenates of the rat cerebral cortex.
Nilsson
B M
BM
Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Center, University of Uppsala, Sweden.
Ringdahl
B
B
Hacksell
U
U
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D008297:Male; D008958:Models, Molecular; D010095:Oxotremorine / Q000031:analogs & derivatives*; D010276:Parasympatholytics / Q000138:chemical synthesis*; D010277:Parasympathomimetics / Q000138:chemical synthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013329:Structure-Activity Relationship; D047090:beta-Lactams
D010276:Parasympatholytics; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D047090:beta-Lactams; D010095:Oxotremorine